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Lim, Kayeong
유전체 교정 연구단
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Identification of Novel Genes for Cell Fusion during Osteoclast Formation

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Title
Identification of Novel Genes for Cell Fusion during Osteoclast Formation
Author(s)
Cho, Eunjin; Cheon, Seongmin; Ding, Mina; Kayeong Lim; Park, Sang-Wook; Park, Chungoo; Lee, Tae-Hoon
Publication Date
2022-06
Journal
International Journal of Molecular Sciences, v.23, no.12
Publisher
MDPI
Abstract
Osteoclasts are derived from hematopoietic stem cells. Monocyte preosteoclasts obtain resorbing activity via cell–cell fusion to generate multinucleated cells. However, the mechanisms and molecules involved in the fusion process are poorly understood. In this study, we performed RNA sequencing with single nucleated cells (SNCs) and multinucleated cells (MNCs) to identify the fusion‐specific genes. The SNCs and MNCs were isolated under the same conditions during osteo-clastogenesis with the receptor activator of nuclear factor‐κB ligand (RANKL) administration. Based on this analysis, the expression of seven genes was found to be significantly increased in MNCs but decreased in SNCs, compared to that in bone marrow‐derived macrophages (BMMs). We then gen-erated knockout macrophage cell lines using a CRISPR‐Cas9 genome‐editing tool to examine their function during osteoclastogenesis. Calcrl‐, Marco‐, or Ube3a‐deficient cells could not develop mul-tinucleated giant osteoclasts upon RANKL stimulation. However, Tmem26‐deficient cells fused more efficiently than control cells. Our findings demonstrate that Calcrl, Marco, and Ube3a are novel determinants of osteoclastogenesis, especially with respect to cell fusion, and highlight potential targets for osteoporosis therapy.
URI
https://pr.ibs.re.kr/handle/8788114/12257
DOI
10.3390/ijms23126421
ISSN
1661-6596
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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